Significance Simian immunodeficiency virus infection of newborn and infant macaques is a useful animal model of human AIDS to evaluate the antiviral effects and toxicity of novel antiviral drugs such as 9-[2-(Phosphonomethoxy)-propyl]adenine (PMPA). We have previously demonstrated that PMPA is a very potent drug to prevent SIV infection or to treat monkeys with established SIV infection. Prolonged PMPA treatment results in the emergence of PMPA-resistant SIV variants. These PMPA-resistant SIV isolates were highly virulent following inoculation into new animals, but surprisingly, if these animals are being given PMPA, they maintain high virus levels, but stay healthy for a long time. It has been demonstrated in murine models that PMPA has immunomodulatory effects, mainly by enhancement of NK cell activity; if the same is true in rhesus macaques, then this would explain why these animals can survive in the presence of high virus levels. Objectives To evaluate possible immunomodulatory effects of PMPA in juvenile rhesus macaques. Results Seven juvenile macaques are being treated daily with saline injections; after several weeks, 5 animals were switched to PMPA treatment for several weeks. Blood collected by venipuncture is being used for determination of NK cell activity by a standard chromium release assay. Future Directions This experiment is currently still in progress. KEY WORDS PMPA, primate, immunomodulation, natural immunity, natural killer cells FUNDING NIH Grant RR00169, Pediatric AIDS Foundation Grant PG-50853